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      Fibroblast growth factor receptor 3 protein is overexpressed in oral and oropharyngeal squamous cell carcinoma

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          Abstract

          Fibroblast growth factor receptor 3 ( FGFR3) is a member of the fibroblast growth factor receptor tyrosine kinase family. It has been identified as a promising therapeutic target in multiple types of cancer. We have investigated FGFR3 protein expression and FGFR3 gene copy‐numbers in a single well‐documented cohort of oral and oropharyngeal squamous cell carcinoma. Tissue microarray sets containing 452 formalin‐fixed paraffin‐embedded tissues were immunohistochemically stained with an anti‐ FGFR3 antibody and hybridized with a FGFR3 fluorescence in situ hybridization probe. FGFR3 protein expression was correlated with clinicopathological and survival data, which were retrieved from electronic medical records. FGFR3 mRNA data of 522 head and neck squamous cell carcinoma ( HNSCC) were retrieved from The Cancer Genome Atlas ( TCGA). Fibroblast growth factor receptor 3 ( FGFR3) protein was overexpressed in 48% (89/185) of oral and 59% (124/211) of oropharyngeal squamous cell carcinoma. Overexpression of FGFR3 protein was not related to overall survival or disease‐free survival in oral ( HR[hazard ratio]: 0.94; 95% CI: 0.64–1.39; P = 0.77, HR: 0.94; 95% CI: 0.65–1.36; P = 0.75) and oropharyngeal squamous cell carcinoma ( HR: 1.21; 95% CI: 0.81–1.80; P = 0.36, HR: 0.42; 95% CI: 0.79–1.77; P = 0.42). FGFR3 mRNA was upregulated in 3% (18/522) of HNSCC from the TCGA. The FGFR3 gene was gained in 0.6% (1/179) of oral squamous cell carcinoma but no amplification was found in oral and oropharyngeal squamous cell carcinoma. In conclusion, FGFR3 protein is frequently overexpressed in oral and oropharyngeal squamous cell carcinoma. Therefore, it may serve as a potential therapeutic target for FGFR3‐directed therapies in oral and oropharyngeal squamous cell carcinoma.

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          Fibroblast growth factor receptor inhibitors as a cancer treatment: from a biologic rationale to medical perspectives.

          The fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) signaling pathway plays a fundamental role in many physiologic processes, including embryogenesis, adult tissue homeostasis, and wound healing, by orchestrating angiogenesis. Ligand-independent and ligand-dependent activation have been implicated in a broad range of human malignancies and promote cancer progression in tumors driven by FGF/FGFR oncogenic mutations or amplifications, tumor neoangiogenesis, and targeted treatment resistance, thereby supporting a strong rationale for anti-FGF/FGFR agent development. Efforts are being pursued to develop selective approaches for use against this pathway by optimizing the management of emerging, class-specific toxicity profiles and correctly designing clinical trials to address these different issues.
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            Molecular pathways: fibroblast growth factor signaling: a new therapeutic opportunity in cancer.

            The fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) signaling axis plays an important role in normal organ, vascular, and skeletal development. Deregulation of FGFR signaling through genetic modification or overexpression of the receptors (or their ligands) has been observed in numerous tumor settings, whereas the FGF/FGFR axis also plays a key role in driving tumor angiogenesis. A growing body of preclinical data shows that inhibition of FGFR signaling can result in antiproliferative and/or proapoptotic effects, both in vitro and in vivo, thus confirming the validity of the FGF/FGFR axis as a potential therapeutic target. In the past, development of therapeutic approaches to target this axis has been hampered by our inability to develop FGFR-selective agents. With the advent of a number of new modalities for selectively inhibiting FGF/FGFR signaling, we are now in a unique position to test and validate clinically the many hypotheses that have been generated preclinically. ©2012 AACR.
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              Emerging biomarkers in head and neck cancer in the era of genomics.

              Head and neck cancer (HNC) broadly includes carcinomas arising from the mucosal epithelia of the head and neck region as well as various cell types of salivary glands and the thyroid. As reflected by the multiple sites and histologies of HNC, the molecular characteristics and clinical outcomes of this disease vary widely. In this Review, we focus on established and emerging biomarkers that are most relevant to nasopharyngeal carcinoma and head and neck squamous-cell carcinoma (HNSCC), which includes primary sites in the oral cavity, oropharynx, hypopharynx and larynx. Applications and limitations of currently established biomarkers are discussed along with examples of successful biomarker development. For emerging biomarkers, preclinical or retrospective data are also described in the context of recently completed comprehensive molecular analyses of HNSCC, which provide a broad genetic landscape and molecular classification beyond histology and clinical characteristics. We will highlight the ongoing effort that will see a shift from prognostic to predictive biomarker development in HNC with the goal of delivering individualized cancer therapy.
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                Author and article information

                Journal
                Cancer Med
                Cancer Med
                10.1002/(ISSN)2045-7634
                CAM4
                Cancer Medicine
                John Wiley and Sons Inc. (Hoboken )
                2045-7634
                28 December 2015
                February 2016
                : 5
                : 2 ( doiID: 10.1002/cam4.2016.5.issue-2 )
                : 275-284
                Affiliations
                [ 1 ] Department of PathologyUniversity Medical Center Utrecht Heidelberglaan 100 3584 CX UtrechtThe Netherlands
                [ 2 ] Department of Head and Neck Surgical Oncology UMC Utrecht Cancer CenterUniversity Medical Center Utrecht Heidelberglaan 100 3584 CX UtrechtThe Netherlands
                [ 3 ] Department of Otorhinolaryngology – Head and Neck SurgeryUniversity Medical Center Utrecht Heidelberglaan 100 3584 CX UtrechtThe Netherlands
                [ 4 ] Department of Molecular CarcinogenesisNetherlands Cancer Institute Plesmanlaan 121 1066 CX AmsterdamThe Netherlands
                Author notes
                [*] [* ] Correspondence

                Stefan Willems, Department of Pathology , University Medical Center Utrecht, H4.2.41 , Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. Tel: +31 (0) 88 755 6568; Fax: +31 (0) 88 756 9593; E‐mail: s.m.willems-4@ 123456umcutrecht.nl

                Article
                CAM4595
                10.1002/cam4.595
                4735780
                26711175
                9ac1b117-346e-40db-8f42-1e6f2347f13c
                © 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 07 August 2015
                : 06 October 2015
                : 28 October 2015
                Page count
                Pages: 10
                Funding
                Funded by: Dutch Cancer Society
                Award ID: 2011–4964
                Categories
                Original Research
                Clinical Cancer Research
                Original Research
                Custom metadata
                2.0
                cam4595
                February 2016
                Converter:WILEY_ML3GV2_TO_NLMPMC version:4.7.6 mode:remove_FC converted:02.02.2016

                Oncology & Radiotherapy
                fibroblast growth factor receptor 3,oral cancer,oropharyngeal cancer,therapeutic target

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